Consistency Evaluation Of Generic Nifedipine Sustained-release Preparations And Metformin Hydrochloride Enteric-coated Preparations By Dissolution Test Combined With GastroPlus Software

Objective:It is to evaluate the quality consistency of generic nifedipine sustained-release preparations and metformin hydrochloride enteric-coated preparations by in vitro dissolution,GastroPlus software simulation,or in vivo bioavailability test,Then,predictive dissolution methods are expected to be developed for the two types of preparations,based on in vitro and in vivo correlationship study.Methods:1.Study on in vitro dissolution and virtual bioequivalence of nifedipine sustained release tabletsIn vitro dissolution curves of six commercially available nifedipine sustained/controlled-release preparations were determined according to the dissolution method included in the Chinese Pharmacopoeia,the US Pharmacopoeia and the Japanese Orange Book.The similarity factor f2 values of the dissolution curves under specified conditions were calculated for any two preparations.Four sustained release preparations were selected,and the in vitro and in vivo correlation and virtual bioequivalence evaluation were carried out by GastroPlus software.2.In vitro dissolution,in vivo relative bioavailability,in vitro-in vivo correlation study of metformin enteric coated tabletsThree kinds of metformin enteric preparations were selected and their dissolution curves under different conditions were determined by the basket method.The bioequivalence of three preparations was determined among six healthy volunteers after a single oral dose of 500 mg metformin enteric preparations according to a simple three-way crossover design.IVIVC study was made by GastroPlus software.Results:1.The dissolution behaviors of two kind of nifedipine controlled-release tablets were similar in three different media.While four kinds of nifedipine sustained-release tablets showed different dissolution behaviors under the dissolution conditions defined in Chinese Pharmacopoeia and Japanese orange paper.Compared to Japanese method,Chinese Pharmacopoeia method for the dissolution of primary nifedipine sustained release tablets gave a better in vitro and in vivo correlation.GastroPlus software combined with the in vitro dissolution data obtained by Chinese Pharmacopoeia gave similar simulated absorption curves of four nifedipine sustained-release tablets,which indicated that the four preaprations were virtual bioequivalence.2.The dissolution behaviors of the three metformin hydrochloride enteric-coated preparations in three examined dissolution media were significantly different.The main pharmacokinetic parameters of 6 healthy male Chinese volunteers after a single oral dose of 500 mg metformin hydrochloride enteric-coated preparations were as follows:tmax were(4.583 ± 1.158)h,(4.917 ± 0.861)h and(7.000 ± 2.000)h,Cmax(1.543 ±0.646)?g·mL-1,(1.189 ± 0.249)?g·mL-1 and(0.808 ± 0.406)?g·mL-1,AUC0-24h(7.311 ±2.192)?g·h·mL-1,(6.253 ± 2.149)?g·h·mL-1 and(5.304 ± 3.364)?g·h·mL-1,respectively.There was no bioequivalence between any two praparations.The in vitro and in vivo correlationship was poor for the studied metformin hydrochloride enteric-coated preparations.Conclusion:1.The dissolution method collected in the Chinese Pharmacopoeia is more applicable for the consistency evaluation of nifedipine sustained-release formulations for its better in vitro and in vivo correlation.The in vitro dissolution curves of the four nifedipine sustained-release tablets were not similar but the simulated in vivo absorption behaviors were similar.2.In vitro dissolution and in vivo absorption results of three domestic metformin enteric-coated preparations are all different significantly and it is difficult to establish in vitro and in vivo correlation.So domestic metformin enteric-coated preparations have high bioinequivalence risk and the quality consistency must be evaluated by human trials.